Organ culture methods have recently been applied in this laboratory which permit survival of human rectal biopsies for 24-48 hours. During the culture period, mucosal structure is preserved, epithelial cell proliferation and migration continue and protein, mucleoprotein and glycoprotein synthesis persist at steady state levels. We will utilize this organ culture technique to study epithelial cell proliferation and migration and protein and glycoprotein synthesis and secretion in normal and in precancerous and cercerous colonic mucosal tissue. Epithelial cell proliferation will be studied by adding 3H-thymidine to the culture medium. Proliferation and migration rates will be compared in rectal biopsies from normal volunteers and from patients with active and quiescent ulcerative colitis, adenomatous polyps, villous adenomas and rectal carcinomas. By adding other appropriate precursor isotopes to the media, protein and glycoprotein synthesis and secretion will be quantitated. We will attempt to develop a bioassay system utilizing the organ culture technique to evaluate directly the effects of cancer chemotherapeutic agents on cell proliferative and synthetic activity in normal and neoplastic colonic tissue. Such in vitro testing should permit more direct definition of the mechanism of action of these drugs. Such testing may eventually permit in vitro determination of sensitivity of a specific colonic neoplasm to a specific chemotherapeutic agent. Correlative studies of glycoprotein synthesis and metabolism in normal, premalignant and malignant human colonic tissue will also be carried out at the cellular and subcellular level, i.e., glycosyltransferase enzyme patterns will be studied in membrane preparations from the above tissues. Sera from normal patients and patients with premalignant and malignant colonic disease will be analyzed for colon derived enzymes involved in glycoprotein synthesis. Similar studies of glycoprotein metabolism and synthesis will be conducted in control rats and rats with colon cancer induced by 1-2 dimenthylhydrazine.